Submissions for variant NM_000094.4(COL7A1):c.3809C>T (p.Pro1270Leu)

gnomAD frequency: 0.00020  dbSNP: rs145068043

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000935073	SCV001080812	likely benign	not provided	2024-11-21	criteria provided, single submitter	clinical testing
Biomedical Innovation Departament, CIEMAT	RCV001352809	SCV001547304	uncertain significance	Epidermolysis bullosa dystrophica	2024-05-13	criteria provided, single submitter	research
GeneDx	RCV000935073	SCV003842884	uncertain significance	not provided	2022-09-16	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the X position in the canonical Gly-X-Y repeat. Although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease.; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003489971	SCV004241030	likely benign	not specified	2024-11-26	criteria provided, single submitter	clinical testing	Variant summary: COL7A1 c.3809C>T (p.Pro1270Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 1614026 control chromosomes, predominantly at a frequency of 0.0044 within the East Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in COL7A1 causing Dystrophic Epidermolysis Bullosa, Recessive phenotype. c.3809C>T has been reported in the literature in individuals affected with Dystrophic Epidermolysis Bullosa, Recessive (Breitenbach_2015, Savostyanov_2022), and one case was reported as compound heterozygous with a (likely) pathogenic variant. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26612796, 36430820). ClinVar contains an entry for this variant (Variation ID: 757455). Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc.	RCV001272615	SCV001454725	likely benign	Epidermolysis bullosa dystrophica inversa, autosomal recessive	2020-01-04	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003970591	SCV004785927	likely benign	COL7A1-related disorder	2022-11-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).